Single-cell RNA sequencing methods can profile the transcriptomes of single cells but cannot preserve spatial information. Conversely, spatial transcriptomics assays can profile spatial regions in tissue sections but do not have single-cell resolution.
Here, Runmin Wei (Siyuan He, Shanshan Bai, Emi Sei, Min Hu, Alastair Thompson, Ken Chen, Savitri Krishnamurthy & Nicholas E. Navin) developed a computational method called CellTrek that combines these two datasets to achieve single-cell spatial mapping through coembedding and metric learning approaches. They benchmarked CellTrek using simulation and in situ hybridization datasets, which demonstrated its accuracy and robustness.
They then applied CellTrek to existing mouse brain and kidney datasets and showed that CellTrek can detect topological patterns of different cell types and cell states. They performed single-cell RNA sequencing and spatial transcriptomics experiments on two ductal carcinoma in situ tissues and applied CellTrek to identify tumor subclones that were restricted to different ducts, and specific T-cell states adjacent to the tumor areas.
Advances in multi-omics have led to an explosion of multimodal datasets to address questions from basic biology to translation. While these data provide novel opportunities for discovery, they also pose management and analysis challenges, thus motivating the development of tailored computational solutions. `muon` is a Python framework for multimodal omics.
It introduces multimodal data containers as `MuData` object. The package also provides state of the art methods for multi-omics data integration. `muon` allows the analysis of both unimodal omics and multimodal omics.
The development of large-scale single-cell atlases has allowed describing cell states in a more detailed manner. Meanwhile, current deep leanring methods enable rapid analysis of newly generated query datasets by mapping them into reference atlases.
expiMap (‘explainable programmable mapper’) Lotfollahi, Mohammad, et al. is one of the methods proposed for single-cell reference mapping. Furthermore, it incorporates prior knowledge from gene sets databases or users to analyze query data in the context of known gene programs (GPs).
Single-cell RNA-seq datasets in diverse biological and clinical conditions provide great opportunities for the full transcriptional characterization of cell types.
However, the integration of these datasets is challeging as they remain biological and techinical differences. **Harmony** is an algorithm allowing fast, sensitive and accurate single-cell data integration.
CellTypist is an automated cell type annotation tool for scRNA-seq datasets on the basis of logistic regression classifiers optimised by the stochastic gradient descent algorithm. CellTypist allows for cell prediction using either built-in (with a current focus on immune sub-populations)or custom models, in order to assist in the accurate classification of different cell types and subtypes.
CellTypist can identify 101 cell types or states from more than one million cells, including previously underappreciated cell states.
For the CellTypist pre-trained models, immune cells from 20 tissues of 19 studies were collected and harmonized into consistent labels. These cells were split into equal-sized mini-batches, and these batches were sequentially trained by the l2-regularized logistic regression using stochastic gradient descent learning. Feature selection was performed to choose the top 300 genes from each cell type, and the union of these genes was supplied as the input for a second round of training.